title: Microcephaly thin corpus callosum intellectual disability syndrome caused by mutated TAF2.
abstract: BACKGROUND
  The combination of microcephaly, pyramidal signs, abnormal corpus callosum, and intellectual disability presents a diagnostic challenge. We describe an autosomal recessive disorder characterized by microcephaly, pyramidal signs, thin corpus callosum, and intellectual disability.
  
  
  METHODS
  We previously mapped the locus for this disorder to 8q23.2-q24.12; the candidate region included 22 genes. We performed Sanger sequencing of 10 candidate genes; to ensure other genes in the candidate region do not harbor mutations, we sequenced the exome of one affected individual.
  
  
  RESULTS
  We identified two homozygous missense changes, p.Thr186Arg and p.Pro416His in TAF2, which encodes a multisubunit cofactor for TFIID-dependent RNA polymerase II-mediated transcription, in all affected individuals.
  
  
  CONCLUSIONS
  We propose that the disorder is caused by the more conserved mutation p.Thr186Arg, with the second sequence change identified, p.Pro416His, possibly further negatively affecting the function of the protein. However, it is unclear which of the two changes, or maybe both, represents the causative mutation. A single missense mutation in TAF2 in a family with microcephaly and intellectual disability was described in a large-scale study reporting on the identification of 50 novel genes. We suggest that a mutation in TAF2 can cause this syndrome.
authors.affiliation: Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: Hellman-Aharony
authors.forename: Pola
authors.initials: P
authors.lastname: Smirin-Yosef
authors.forename: Ayelet
authors.initials: A
authors.lastname: Halevy
authors.forename: Metsada
authors.initials: M
authors.lastname: Pasmanik-Chor
authors.forename: Adva
authors.initials: A
authors.lastname: Yeheskel
authors.forename: Adi
authors.initials: A
authors.lastname: Har-Zahav
authors.forename: Idit
authors.initials: I
authors.lastname: Maya
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.forename: Dvir
authors.initials: D
authors.lastname: Dahary
authors.forename: Ami
authors.initials: A
authors.lastname: Haviv
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
mesh_terms: D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019295:Computational Biology; D003337:Corpus Callosum / Q000473:pathology*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006639:Histidine / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000150:complications / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D011392:Proline / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics*; D035362:Transcription Factor TFIID / Q000235:genetics*
chemical_list: C486221:TAF2 protein, human; D035381:TATA-Binding Protein Associated Factors; D035362:Transcription Factor TFIID; D006639:Histidine; D011392:Proline
keywords: Microcephaly syndrome; TAF2; autosomal recessive; corpus callosum; pyramidal